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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
Abstract<sec> <title>Background

Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.

Methods

Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 163 patients. Their functional role in drug sensitivity was assessed in vitro.

Results

We identified 490 DMRs following exposure to therapy, of which 31 were CLL-specific and independent of changes occurring in normal B-cell development. Seventeen DMR-associated genes were identified as differentially expressed following treatment in an independent cohort. Methylation of the HOXA4, MAFB and SLCO3A1 DMRs was associated with post-treatment patient survival, with HOXA4 displaying the strongest association. Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib.

Conclusion

Our study demonstrates enrichment for multiple CLL-specific epigenetic traits in response to chemotherapy that predict patient outcomes, and particularly implicate epigenetic silencing of HOXA4 in reducing the sensitivity of CLL cells to therapy.

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Publication Date
Wed Oct 01 2008
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Survival of Patients with CML on Imatinib Experience with 44 Iraqi Patients

Background: Chronic myeloid leukemia (CML) is a clonal stem disease with distinctive clinical course which is ultimately fatal. It is characterized by the presence of Philadelphia
chromosome (t 9:22).Tyrosine kinase inhibitors like imatinib mesylate as targeted therapy had revolutionized the management of CML with significant prolongation of overall survival and
decreased rate of blastic transformation.
Objective:This study will describe the experience of treating 44 Iraqi patients with chronic myeloid leukemia by imatinib at the National Hematology Centre in Baghdad.
Patients and Methods:This study included 44 Iraqi patients diagnosed in Chronic phase CML at the National Centre of Hematology in Baghdad fr

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Publication Date
Thu Apr 13 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Estimate Complete the Survival Function for Real Data of Lung Cancer Patients

 In this paper, we estimate the survival function for the patients of lung cancer using different nonparametric estimation methods depending on sample from complete real data which describe the duration of survivor for patients who suffer from the lung cancer based on diagnosis of disease or the enter of patients in a hospital for period of two years (starting with 2012 to the end of 2013). Comparisons between the mentioned estimation methods has been performed using statistical indicator mean squares error, concluding that the survival function for the lung cancer by using shrinkage method is the best

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Publication Date
Tue Oct 20 2020
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Estimating of Survival Function under Type One Censoring Sample for Mixture Distribution

In this article, it is interesting to estimate and derive the three parameters which contain two scales parameters and one shape parameter of a new mixture distribution for the singly type one censored data which is the branch of right censored sample. Then to define some special mathematical and statistical properties for this new mixture distribution which is considered one of the continuous distributions characterized by its flexibility. Next,  using maximum likelihood estimator method for singly type one censored data based on the Newton-Raphson matrix procedure to find and estimate values of these three parameter by utilizing the real data taken from the National Center for Research and Treatment of Hematology/University of Mus

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Publication Date
Tue Mar 10 2020
Journal Name
Open Access Macedonian Journal Of Medical Sciences
Functional Outcome Following Synthetic Vertebral Body Implantation in the Management of Spinal Disorders

OBJECTIVE: Synthetic vertebral body replacement has been widely used recently to treat different spinal conditions affecting the anterior column. They arrange from trauma, infections, and even tumor conditions. In this study, we assess the functional outcome of this modality in different spinal conditions. PATIENTS AND METHODS: Thirty-six cases operated from October 2010 to December 2017. Twelve patients had spinal type A3 fractures, 11 cases with spinal tuberculosis (TB), and 13 cases with spinal tumors. They were followed clinically for a mean period of 2.4 years. RESULTS: All the cases were approached anteriorly. Seven cases had a post-operative infection. No neurological worsening reported. We had dramatic neurologic

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Publication Date
Thu Nov 23 2017
Journal Name
Brazilian Journal Of Analytical Chemistry
Microvolume-DLLME for the Spectrophotometric Determination of Clidinium Bromide in Drug, Urine, and Serum

The present study combines UV-Vis spectrophotometry and dispersive liquid-liquid microextraction (DLLME) for the preconcentration and determination of trace level clidinium bromide (Clid) in pharmaceutical preparation and real samples. The method is based on ion-pair formation between Clid and bromocresol green in aqueous solution using citrate buffer (pH = 3). The colored product was first extracted using a mixture of 800 µL acetonitrile and 300 µL chloroform solvents. Then, a spectrophotometric measurement of sediment phase was performed at λ = 420 nm. The important parameters affecting the efficiency of DLLME were optimized. Under the optimum conditions, the calibration graphs of standard -1 (Std.), drug, urine and serum were ranged

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Publication Date
Wed Mar 15 2023
Journal Name
Journal Of Medicinal And Chemical Sciences
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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Comparing the Efficacy of Paracetamol, Diclofenac, and Ketorolac on Post-Appendectomy Outcomes in Children and Adolescents

Abstract

urgent surgical intervention and appendectomy until now represent standard treatment for uncomplicated cases of appendicitis. Nausea, vomiting and pain after surgery are the most frequent issues facing patients and affecting patient quality of life and responsible for many cases of readmission after surgery. Ketorolac and diclofenac represent the most commonly prescribed non-steroidal anti-inflammatory used in postoperative setting and they cause many side effects as gastrointestinal, kidney and cardiac adverse effect in addition to increased risk of bleeding. Paracetamol is currently among the most frequently prescribed medication worldwide and it can be used safely for all age groups. This study aimed

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Publication Date
Sat Dec 30 2023
Journal Name
Iraqi Journal Of Science
Continuous Flow Injection Analysis for The Photometric Determination of Metformin Drug Via The Release of Copper(II) ion from Charged Gel Bead Crystal

A newly developed analytical method characterized by its speed and sensitivity for the determination of metformin-HCl via the formation of complex for metformin-HCl-OH--copper(II) ion from the gel bead system by continuous flow injection analysis. The method is based on the imbedded copper(II) ion in the gel bead structure can be used in the reaction for the formation of red –magneta colour complex(λmax. =530nm) formed by direct reaction of the drug with the released copper (II) ion from the gel bead in alkaline medium. Linear dynamic range for the absorbance versus metformin concentration was 0.001-1 mmol.L-1 while C.O.D was (r2% =95.33%) . The L.O.Q was 0.868mmol.L-1.L.O.D (S/N=3)=0.5μmol.L-1 from the step wise dilution for the min

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Publication Date
Wed Nov 20 2024
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of Periodontal Therapy on Serum and Salivary Interleukin-2 Levels in Chronic Periodontitis

Background: Interleukine-2 is a multifunctional cytokine, considered a central regulator of host resistance against a variety of pathogens and has been recently demonstrated to exert an active role in the pathogenesis of periodontal diseases. The purpose of this study was to evaluate the effect of scaling and root planning on level of IL-2 in serum and saliva of patients with chronic generalized periodontitis, in relation to clinical parameters. Materials and Methods: A total of 50 subjects were enrolled, of which 25 had chronic generalized periodontitis and 25 periodontally healthy subjects as control. The clinical parameters included: gingival index, pocket probing depth, clinical attachment level and bleeding on probing. The level of

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Publication Date
Thu Jan 01 2026
Journal Name
Open Journal Of Medicinal Chemistry